Sclerosing composition



Patented Feb. 14, 1950 SCLEROSING COMPOSITION Laszlo Reiner, Bloomfield, N. J assignor to Wallace & Tiernan Products, Inc., Belleville, N. J a corporation of New Jersey No Drawing. Application December 9, 1947, Serial No. 790,713

4 Claims. 1

This invention relates to a sclerosing composition for injection into the human or animal body for the purpose of obliterating cavities and producing fibrosis.

The invention is particularly useful in connection with the treatment of varicose veins and will be illustrated by detailed description in connection with treatment of this common ailment.

Varicose 'veins aiflict many elderly persons, particularly women. The closing of the venous valves becomes impaired, the smooth muscles and fibers of the veins are weakened through the resulting increased pressure of the blood, and, due to the slowness of the flow of the blood through these veins, clotting of blood sometimes occurs in the veins. This is followed too frequently by infection and sometimes by ulceration. In general, conditions following the clotting of the blood accompanying varicose veins are known as thrombosis, thrombophlebitis, and variscole ulcers.

A surgicial treatment for varicose veins includes the production of an artificial sterile adherent clot of blood (thrombosis) in the vein with subsequent fibrosis, so as to obstruct or close the weakened section of the vein. A by-pass then slowly develops for the venous blood, the bypass connecting with the original vein at a point beyond the obstruction produced by the sterile thrombosis.

To produce this thrombosis, there has been proposed heretofore a number of chemical solutions which irritate the intima of the veins and develop a condition causing deposition of the fibrin of the blood. These irritating chemicals that have been proposed include rather concentrated solutions of dextrose, sucrose, or salt, all used at strongly hypertonic concentrations; quinine or urethane, which are protoplasma poisons; and also soluble salts of unsaturated organic acids of high molecular weight, particularly in the form of alkaline solutions of the salts of the acids with an alkali metal or an amine.

All these solutions that have been proposed are destructive to living tissues and may affect not alone the intima of the veins, but also the entire wall of the veins and the adjacent tissue. Such destruction results not infrequently in localized gangrenes. In addition, some of these chemicals are derived from natural sources and contain allergens which produce local and systemic reactions that are undesirable with patients allergric to the substances present.

The present invention provides a sclerosing composition which is free from objections res'ulting from the use of alkaline or hypertonic solutions, does not contain allergens, and at the same time produces an exceptionally strong sclerosing action and uniform thrombosis. As a result of this thorough sclerosing action, there is a minimized tendency for recanalization of the weakened portions of the veins. In addition the present composition is simple, relatively inexpensive, and not dependent upon natural sources of raw materials such as quinine, unsaturated fatty acids of cod liver oil, or the like.

Briefly stated, the invention comprises a sclerosing composition which is a sterilized clear solution and consists essentially of a carrier that is largely water and a sclerosing agent consisting of a water-soluble non-toxic salt giving a surface active anion when dissolved in the carrier. Specifically the stated salt is an organic sulfate or sulfonate including a cationic constituent, the other constituent (linked to 0803- or -S0r) being a chain composed of one or more aliphatic hydrocarbon. residues and one or more residues that provide links (in the stated chain) of a selected character other than -CH2 or ----CH:;. Branched chain alkyl sulfates containing at least 6 and quite preferably 10 carbon atoms or more are particularly important representatives of the stated class of water-soluble, non-toxic salts; other members of the class are the corresponding sulfonates, and sulfates or sulfonates containing mixed groups, instances of the latter being alkaryl sulfates and sulfonates, containing at least 10 carbon atoms.

An example of the composition of the present invention is a solution of purified sodium tetradecylsulfate in water, the sulfate being identified more exactly as sodium Z-methyl-V-ethylundecyl-4 sulfate. This material is used in the concentration of 1 to 5 parts for parts total weight of its solution in distilled Water.

Proportions here and elsewhere herein are expressed as parts by weight unless specifically stated to the contrary.

The whole composition is sterilized.

It is theninjected intravenously at a position adjacent to the section of the varicose vein that is to be treated and on the side of that section away from the heart, so that the movement of the blood towards the heart distributes the iniected composition over the weakened tissue of the vein. This causes the desired thrombosis. The injection is repeated on a number of different days, ordinarily 5 to 15 times, to produce the complete effect desired. It should be understood that other methods used for the sclerosing therapy of veins, including so-called retrograde injection, i. e. against the normal flow of blood, may also be employed to efiect such therapy with compositions of the present invention.

Clinical tests with this material have been made on a very large number of human cases,

including over 750 reported from two sources,

alone. All of the-reports have been very satisfactory. A number of the physicians making these tests state that the composition is superior" to any other sclerosing composition that they have used in (1) correcting more difiicult cases, (2) producing results rapidly,and (3) being more nearly universally effective.

It is not to be inferred that such uniformly sa isfactory results will always .be found in the future, but the results given are representative; of what has been found to date and reported to me. It is to be understood in any case'thatthe treatment and medicines herein described are not-to be used. except by; or on the order of a physician or surgeon.

.As the carrier there is noalternative, for water. There may be presentin the water materials ordinarily. present in intravenous injections. Thus, there may be used aqueous solutions; of: dextrose, sucrose, salt or the like,.preferablyof isotonic non-sclerosing concentration and of a compositionwhich is inert to the sclerosing agent. These, however, are not necessary; In addition there may be used in the carrier other admixtures as, for instance, mild-local-anesthetics and antiseptics in amounts that-although minor are substantial, that is, adequate toimpart to the whole composition the desired anesthetic or= antiseptic property. Examples of-such materials are trichlorobutanol' which is sometimes known as chl'oretone andbenzyl alcohol added, for example, in the proportionv of about 2 partsto 100 parts of the whole composition as injected.

Itis believed that the carrier causes distribue tion'ofthe sclerosing agent as a thin film over the surface tobe treated, moderates the rate of initial action, and promotes: uniformity of thrombosis.

According to present understanding; the composition including the carrier andmy sclerosing agent need notube irritating'to producethe desired thrombosis and, infact, is preferably made substantially non-irritating; 'It' appears. importantthat the pH be adjusted" within; the range of about? to8, advantageously between 7 and 7.8 and for optimum results toabout 713 beforeinjection. Accordingly Ipreadjust-the-pH of my composition, asnecessary, to a-value of the; stated character and. to the extentthat the composition (i. e. the sclerosing-solution) doesv not inherently have the desired pH, such--pre-adiustment is effected withthe aid: of a suitable buffer, for instance by the addition of a. sodium phosphate such as secondary sodium phosphate, sodium carbonate, or-the salt of aweak organic acid with a strong base of which sodium citrate is an example.

The sulfate or sulfonicacid compound to be incorporated with the aqueous medium to form the sclerosingcomposition and sometimes .referred to-herein as the sclerosing agent should be water-soluble and non-toxic in the proportions used. It should-be free from impurities or materials, that, if present, interfere, with the desired; efiect or produce untoward symptoms.

Thus the sclerosing composition, which is sterileand whichis adjusted to or: otherwise characterized. by'the-specified'pI-I;contains; the. carrier.

:and at least; one residue selected from the class consisting: of hydroaromatic radicals, -'CH-R -O, -S--, --COO--, CONH-, and B being an alkyl radical, R

being-a short chain alkyl radical containing less than 6 carbon atoms, the divalent hydrocarbon residues, CHR and divalent hydroaromatic residues being linked to at .--least one and the other divalent residues being linked to two carbon atoms, and-said chain consi'sting of residues of the. aliphatichyd-rocarbon and of the'other aforesaid class. That isto say, the constituent R is achain composed of one ormore aliphatic hydrocarbon residues. and one or-"moreresidues of the other: stated class; and it should ordinarily contain at least 1 .0; carbon atoms;--except: as otherwise indicated herein, for example in1thatthe compound R --XM, may bea branched chain alkylisulfate haying six or morescarbon atoms.

It may berspecifically' noted: that the constituent:- +X--.isconnected to a. carbonatom of a hydrocarbon residue in R1, i-.je. to a carbon. atom of a hydroaromaticradical, or'of -CHR or of 'anyrother aliphatic-hydrocarbon residue. Furthermore, each divalent residue. (in R haseach ofitsvalences which isnot connected to X; connected tQra carbon: atom.

It will. be understood: that. the. indicated con,- nection between the component X and the componentR, may extend from X to a terminal link inthe chain. cons-titutingiR or it may extend to'an; intermediate link, i. e. an atom which canpbe considered as other than an end of the chain-R It will also be appreciated, of course, thatit;isiimmaterialiwhether :a compound wherein an alkyl' radicalwisalinkedzto-- X through a residue -CHR'+-i's considered: (a) as having X connected to an intermediate link of the= complete chainRF (which includesR l; or (b) as having Ri constituted byabranched chain alkyl radical-with ,-X connected at" the end from which thebranches' extend. Considered either way; the compound (if otherwise satisfying the stated, requirements) comeswi-thin. the defined class of: the. invention.

It: will be appreciated that the salt' R "-X -M of the described. constitution. represents anum.- ber of "compounds having the desired characteristics and properties. For instancawhere the selected other; residue is -CHR the salt may be arbranched: chain alkyli sulfate (or sulfonate),cex-ainples of R in thatcaseibei'ngz 2- methyl' 7. --ethylundecyl;1 3 butyldelcyl; and: 2,6 ,10,14,- tetramethylhexad'ecenyl. Likewise where the aliphatichydrocarbonresidue: is linkedto the component X, by a hydroaromatic radical; the: compound may be an. alkaryl sulfate or: sulfonate; examplesof these'orlike-groups. for R are p;-isoo.ctylphenyl andi p-.isopropylphenyloctyl. Furtherinstances ofresidues which maybe represented by R providin'gralkaryli compounds, are (a); tetrahydronaphthalene,v (#11): phencyclohep- 76 tanaq-and (c amylindan; each. less." a hydrozem Formulas for sulfonic acids of groups of the last three kinds, in order, are given below:

RQqSC-I OHzOH CH2 +5 0.

CH2CH V GH CaHu( J 5 (L2 It will also now be. understood that R may represent components having the character of the specific alkyl and alkaryl types mentioned above and may include other interrupting links, i. e. introduced groups or atoms from the stated class of residues, and likewise may represent other combinations of alkyl groups with hydroaromatic or other specified residues, or both. Further particular instances of various salts within the defined class of sclerosing agents are included in the examples, enumerated below, of compositions according to the present invention.

Thus an instance of a compound wherein R includes several aliphatic hydrocarbon residues and also residues of at least two kinds selected from the class recited hereinabove, is a substance such as named in Example 5 below, having the formula:

wherein R is a branched chain alkyl radical (i. e.

including the residue -CHR In the case of compounds such as the sulfosuccinates it has been noted that better sclerosing activity has generally been obtained where R is a branched chain alkyl group rather than where it is, for instance a straight chain isomer of such group.

The selected compound is dissolved in water to a concentration of 1 to 10 parts for 100 parts of the finished solution; the amount of the compound is preferably kept in the range of 1 to 5 parts in cases ordinarily met in practice. The concentration to be used depends on the efiectiveness of the particular compound as well as on the type of lesion which is being treated with it. Small lesions located in tender parts of the animal or human body require lower concentrations than large lesions. Compositions containing as low as about one-half of one part for 100 parts of the finished solution have been found to have some utility, for sclerosing purposes; although as indicated, present medical experience is that the stated stronger concentrations are usually of markedly greater value. After sterilization, the solutions are retained in sterile vials or other containers until used.

The technique of administration is that which is well known to those skilled in the art of human and veterinary medicine. Thus it is necessary to vary the amount of solution to be injected The injection inhumane ordinarily requires 05 to 20 cc. of the solution. In rabbits the dosage runs ordinarily between 0.05 and 0.2 cc. In dogs good results have been obtained with 0.5 to 10 cc. of solutions containing 1.5% to 7% of the dissolved salt of the organic sulfate or sulfonic acid.

The sclerosing composition, in addition to the many tests on humans, has been bio-assayed as follows:

A standard volume (0.05 cc.) of various dilutions of the sclerosing composition are injected into the tail vein of mice, at a position about 45 mm. from the base of the tail. The length of the thrombus in the vein is measured after 3 days, 7 days and 14 days. A number of mice, suitably about 10, are used for each dose level. The average length of the thrombus resulting is then plotted against the logarithm of the concentration of the solution used.

With such bio-assay method, I have found that the water soluble salts of the kind described herein are effective in giving thrombi ranging from about 10 to 45 mm. in length and in fact in some instances up to the full distance from the position of injection to the base of the tail.

My substantially neutral solution of sodium tetradecylsulfate, for instance, when assayed in this manner, at concentrations varying from 0.125% to 2% of the total weight of the aqueous solution, was at least stronger than sodium ricinoleate of the same concentration in spite of the greater alkalinity of the latter. Also my organic sulfate produced a definite thrombus at concentrations as low as 0.125% whereas the sodium ricinoleate required 0. 5% as the threshhold concentration.

Once the results obtained with my composition have been observed, various theories may be advanced to explain the mechanism of the action.

It is considered that the results are due in large measure to the formation of a very thin film of the sclerosing composition over the inside wall of the cavity to be obliterated. It is also believed that the nature of'the chemical substance as hereinabove defined and as embodied in the present invention affords a distinct difference from other compounds now being used for sclerosing therapy with respect to the specific area which the chemical substance covers when adsorbed in the film extending over the said wall, the combined results of these effects being conducive to the clotting of blood and deposition of fibrin or other protein of blood in the cavities to be obliterated.

according to the size of the vessel or cavity and The invention will be further illustrated in connection with the following specific examples of making my improved sclerosing composition.

Ea'ample 1 Fifty parts of sodium tetradecylsulfate (sodium 2-methy1-7-ethylundecyl-4 sulfate, a highly puri fied form of an available product known as Tergitol 4) are dissolved in 1,000 parts of distilled water. A small proportion of sodium phosphate or monosodium phosphate is added as a butter to establish the pH at approximately '7, the amount of this buffer required in this instance being ordinarily practically negligible with respect to its efiect on the sclerosing action. The solution so made is filled. into vials which are sealed or stoppered and then sterilized. by auto clavin g for 15 minutes at 15 lbs. gage steam pressure. The sterilized containers and solution are then allowed to cool and retained until ready for use.

Example 2 Thirty parts of sodium tetradecyl sulfate ofthe kind described and 20 parts of benzyl alcoholas a local anesthetic are dissolved in 1,000 parts of distilled water. The solution is vialed and .then sterilized at 10 lbs. gage steam pressure for onehalf'hour.

Example 3 Fifty parts of the sodium salt of tetrahydronaphthalene sulfonate in purified condition'and 5 parts of trichlorbutanol as an antiseptic are dissolved in 1,000 parts of distilled water. The pH-is adjusted to a value between 7 and 7.8 by the addition of an aqueous solution of monosodium phosphate or disodium phosphate. The resulting sclerosing composition is enclosed in vials and sterilized asabove.

Ewample 4 Onehundredparts of a purified productiknown as Igepon and having the formula and 5 parts of chlorothymol as antiseptic .are dissolved in 1,000 parts of distilled water. The resulting composition is charged into vials and sterilized as above.

Example 4A Fifty parts of a product called Igepon T, containing 73% of sodium stearylmethylaminoethane sulfonate, and 20 parts of benzyl alcohol are dissolved by the addition of 930 parts of distilled water. The solution is then filtered through a dense Berkefeld filter and charged into sterile CH3(OHZ)IGO ONGHzCHaSOzN'a Example 5 Twenty parts of sodium dioctyl sulfosuccinate :lpurified Aerosol OT) and 10 parts of benzylal- 'cohol are dissolved in 1,000 parts of distilled water. Buffer is added if necessary to establish the pH Within range 7 to 7.8. The solution .is then charged into vials and sterilized for onehalf hour at approximately 1100 C. in an Arnold type of sterilizer.

Example .6

Two hundred parts of a solution of .asubstance known as Merpentine and containing the sodium alkyl naphthyl sulfonate is dissolved in 1,000 parts of distilled water. The formula for sodium alkyl naphthyl (or naphthalene). sulfonate is as follows, R being an alkyl and more specifically The solution is adjusted as to hydrogen ion'concentration to the range stated above and sterilized by heat irradiation or addition of a chemical disinfectant. Examples o such chemical disintectant are phenol, hexylresorcinol, and merthiolate in usual effective but-non-toxic concen trations. I This solution was tested for sclerosing activity by the method described above, and it was found that no obliteration was produced by a solution containing 0.125% of the sclerosing agent; 15.8 mm. average obliteration was produced at the 0.25% level; 18.3mm. average obliteration was produced at the 0.50% level and 41.4 mm. average obliteration was produced by the 1% solution.

Example 7 Three hundred parts of a purified slurry of a product called Triton 720 and containing a 20% solution of an alkali metal salt of an aryl polyether sulfonate in 10 parts of phenol as antiseptic are dissolved in 1 liter of distilled water. In view of the sterilizing effect of the phenol, no heat sterilization is required.

Example 8 Two hundred parts of oleoglycerol sulfate whose active ingredient is an alkenoyl (unsaturated fatty acid residue) glycerol sulfate, is dissolved in 1,000 parts of water. The material is charged into containers and sterilized as described under Example 1 above.

Example 9 Thirty parts of a product called Santomerse D and consisting of sodium decylbenzene sulfonate, isdissolved in 970 parts of pyrogen-free distilled Water and filtered through a dense s'intered glass filter to eliminate suspended particles, pyrogens and other foreign undissolved material. It is then charged into vials and sterilized by autoclaving in the usual manner. The schlerosing activity of this solution when tested in mice was evidenced by the following results: 0.3% solution produced an average obliteration of 4.2 mm; 0.6% produced an average obliteration of 18.4 mm. and 1.2% produced an average obliteration of 18.6 mm. These results indicate that this solution is especially useful in low concentrations for the treatment of very small superficial veins. The :formula for sodium decylbenzene sulfonateis:

Example 10 One hundred parts of an aqueous solution containing 27% of the sodium aryl polyether sulfate is mixed with 5 parts of phenol and 893 parts of pyrogen-free distilled water. The solution is then filled. into containers and sterilized in an Arnold .type of sterilizer.

Aryl (OOC2CH2MOSOsNa The dissolving described in Examples 1 to 10 .gives clear solutions.

It will be understood that it is intended to cover all changes and modifications of the examples of the invention herein chosen for the purpose of illustration which do not constitute departures from thespirit and scope of the invention.

This application is a continuation-in-part of my copending application Serial No. 573,137, filed January 16, 1945 for Sclerosing composition now abandoned.

I claim:

1. A sclerosing sterilized clear solution comprising water as a liquid carrier in the proportion of at least about 98 parts for 100 parts of the carrier, a sclerosing agent dissolved in the water, and a buffer establishing the pH of the whole in the range of about 7 to 8, the scleroslng agent being in the proportion of 1 to 10 parts by weight for 100 parts of the solution, being a water so1uble, non-toxic salt giving a surface active anion when dissolved in the carrier, and being a branched chain aliryl sulfate containing at least six carbon atoms in the alkyl group, and a watersoluble-salt forming component.

2. A sclerosing sterilized clear solution comprising a liquid carrier containing at least about 98 parts of water for 100 parts of total weight of the carrier, a water soluble salt of Z-methyI I-ethylundecylsulfate dissolved in the carrier, and a buiier establishing the pH in the range of about '7 to 8, the proportion of the said water soluble salt being 1 to 10 parts for 100 parts of the whole composition.

3. A product consisting of a sealed, internally sterilized container containing a predetermined quantity of a sterilized, clear, sclerosing solution, said solution being sterilized by application of sterilizing energy after being disposed and sealed in said container, said sterilized, clear solution comprising water as a liquid carrier in the proportion of at least about 98 parts for 100 parts of the carrier, and a sclerosing agent dissolved in the water, said solution having a pH in the range of about *7 to 8, the sclerosing agent being in the proportion of 1 to 5 parts by weight for 100 parts of the solution, being a material giving a surface active anion when dissolved in the carrier, and being a water soluble, non-toxic salt having the formula R X-M wherein M is the cationic constituent of the said salt, wherein X is selected from the group consisting of OSO3 and SO3- and is connected to a carbon atom of a hydrocarbon residue in R and wherein R is an acyclic group containing at least 10 carbon atoms and consisting of a chain of carbon-containing residues of which at least part are hydrocarbon residues, said R comprising at least one branched chain alkyl group having at least six carbon atoms. 4. A product consisting of a sealed, internally sterilized container containing a predetermined quantity of a sterilized, clear solution of a sclerosing agent, said sclerosing solution being sterilized by treatment with a sterilizing agency distinct from said sclerosing agent, and the interior of the container being also sterilized by treatment with such an agency, and the entire interior and contents of the sealed container being in a positively sterilized condition, said sclerosing sterilized clear solution comprising Water as a liquid carrier in the proportion of at least about 98 parts for 100 parts of the carrier, and the aforesaid sclerosing agent dissolved in the water, said solution having a pH in the range of about 7 to 8, the sclerosing agent being in the proportion of to parts by weight for 100 parts of the solution, being a material giving a surface active anion when dissolved in the carrier, and being a water soluble, non-toxic salt having the formula R XM wherein M is the cationic constituent of the said salt, wherein X is selected from the group consisting of OSOa-- and -SO3 and is connected to a carbon atom of a hydrocarbon residue in R and wherein R is a chain containing at least 10 carbon atoms and containing at least one aliphatic hydrocarbon residue and at least one residue selected from the class consisting of hydroaromatic radicals, CHR -O, --S--, CONH and a CONR wherein R is an alkyl radical and R is a short chain alkyl radical containing less than 6 carbon atoms, each divalent residue having each of its valences which is not connected to X, connected to a carbon atom, and said chain consisting of residues of the aliphatic hydrocarbon and of the other aforesaid class.

LASZLO REINER.

REFERENCES CITED The following references are of record in the file of this patent:

Gershenfeld et al., Am. J. Pharm., Aug. 1941, pages 306-326. (Copy in l6'7-85W.)

Certificate of Correction Patent No. 2,497,742 February 14, 1950 LASZLO REINER It is here-lay certified that errors appear in the printed specification of the above numbered patent requiring correctlon as follows:

Column 5, line 5, for that portion of the formula reading $0- read S0 line 15, for $0. read S0 column 8, line 67, for (OOC CH read (OCH OH and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 25th day of July, A. D. 1950.

THOMAS F. MURPHY,

Assistant Gammisaz'oner of Patents. 

4. A PRODUCT CONSISTING OF A SEALED, INTERNALLY STERILIZED CONTAINER CONTAINING A PREDETERMINED QUANTITY OF A STERILIZED, CLEAR SOLUTION OF A SCLEROSING AGENT, SAID SCLEROSING SOLUTION BEING STERILIZED BY TREATMENT WITH A STERILIZING AGENCY DISTINCT FROM SAID SCLEROSING AGENT, AND THE INTERIOR OF THE CONTAINER BEING ALSO STERILIZED BY TREATMENT WITH SUCH AN AGENCY, AND THE ENTIRE INTERIOR AND CONTENTS OF THE SEALED CONTAINER BEING IN A POSITIVELY STERILIZED CONDITION, SAID SCLEROSING STERILIZED CLEAR SOLUTION COMPRISING WATER AS A LIQUID CARRIER IN THE PROPORTION OF AT LEAST ABOUT 98 PARTS FOR 100 PARTS OF THE CARRIER, AND THE AFORESAID SCLEROSING AGENT DISSOLVED IN THE WATER, SAID SOLUTION HAVING A PH IN THE RANGE OF ABOUT 7 TO 8, THE SCLEROSING AGENT BEING IN THE PROPORTION OF 1/2 TO 10 PARTS BY WEIGHT FOR 100 PARTS OF THE SOLUTION, BEING A MATERIAL GIVING A SURFACE ACTIVE ANION WHEN DISSOLVED IN THE CARRIER, AND BEING A WATER SOLUBLE, NON-TOXIC SALT HAVING THE FORMULA R1-X-M WHEREIN M IS THE CATIONIC CONSTITUENT OF THE SAID SALT, WHEREIN X IS SELECTED FROM THE GROUP CONSISTING OF -OSO3- AND -SO3- AND IS CONNECTED TO A CARBON ATOM OF A HYDROCARBON RESIDUE IN R1, AND WHEREIN R1 IS A CHAIN CONTAINING AT LEAST 10 CARBON ATOMS AND CONTAINING AT LEAST ONE ALIPHATIC HYDROCARBON RESIDUE AND AT LEAST ONE RESIDUE SELECTED FROM THE CLASS CONSISTING OF HYDROAROMATIC RADICALS, -CHR2-, -O-, -S-, -CONH- AND -CONR3-, WHEREIN R2 IS AN ALKYL RADICAL AND R3 IS A SHORT CHAIN ALKYL RADICAL CONTAINING LESS THAN 6 CARBON ATOMS, EACH DIVALENT RESIDUE HAVING EACH OF ITS VALENCES WHICH IS NOT CONNECTED TO X, CONNECTED TO A CARBON ATOM, AND SAID CHAIN CONSISTING OF RESIDUES OF THE ALIPHATIC HYDROCARBON AND OF THE OTHER AFORESAID CLASS. 